AUTHOR=Lu Richard , Popov Vsevolod , Patel Jignesh , Eaves-Pyles Tonyia 

TITLE=Burkholderia mallei and Burkholderia pseudomallei stimulate differential inflammatory responses from human alveolar type II cells (ATII) and macrophages

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=2

YEAR=2012

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2012.00165

DOI=10.3389/fcimb.2012.00165

ISSN=2235-2988

ABSTRACT=<p>Alveolar type II pneumocytes (ATII) and alveolar macrophages (AM) play a crucial role in the lung's innate immune response. <italic>Burkholderia pseudomallei</italic> (<italic>BP</italic>) and <italic>Burkholderia mallei</italic> (<italic>BM</italic>) are facultative Gram-negative bacilli that cause melioidosis and glanders, respectively. The inhalation of these pathogens can cause lethal disease and death in humans. We sought to compare the pathogenesis of and host responses to <italic>BP</italic> and <italic>BM</italic> through contact with human primary ATII cells and monocytes-derived macrophages (MDM). We hypothesized that because <italic>BP</italic> and <italic>BM</italic> induce different disease outcomes, each pathogen would induce distinct, unique host immune responses from resident pulmonary cells. Our findings showed that <italic>BP</italic> adhered readily to ATII cells compared to <italic>BM</italic>. <italic>BP</italic>, but not <italic>BM</italic>, was rapidly internalized by macrophages where it replicated to high numbers. Further, <italic>BP</italic>-induced significantly higher levels of pro-inflammatory cytokine secretion from ATII cells (IL-6, IL-8) and macrophages (IL-6, TNFα) at 6 h post-infection compared to <italic>BM</italic> (<italic>p</italic> &lt; 0.05). Interestingly, <italic>BM</italic>-induced the anti-inflammatory cytokine, IL-10, in ATII cells and macrophages at 6 h post-infection, with delayed induction of inflammatory cytokines at 24 h post-infection. Because <italic>BP</italic> is flagellated and produces LPS, we confirmed that it stimulated both Toll-like receptor (TLR) 4 and TLR5 via NF-κb activation while the non-flagellated <italic>BM</italic> stimulated only TLR4. These data show the differences in <italic>BP</italic> and <italic>BM</italic> pathogenicity in the lung when infecting human ATII cells and macrophages and demonstrate the ability of these pathogens to elicit distinct immune responses from resident lung cells which may open new targets for therapeutic intervention to fight against these pathogens.</p>